WO2008067488A9 - Régénération d'une dent fonctionnelle médiée par des cellules souches mésenchymateuses - Google Patents

Régénération d'une dent fonctionnelle médiée par des cellules souches mésenchymateuses

Info

Publication number
WO2008067488A9
WO2008067488A9 PCT/US2007/085971 US2007085971W WO2008067488A9 WO 2008067488 A9 WO2008067488 A9 WO 2008067488A9 US 2007085971 W US2007085971 W US 2007085971W WO 2008067488 A9 WO2008067488 A9 WO 2008067488A9
Authority
WO
WIPO (PCT)
Prior art keywords
scap
root
tooth
carrier
stem cells
Prior art date
Application number
PCT/US2007/085971
Other languages
English (en)
Other versions
WO2008067488A2 (fr
WO2008067488A3 (fr
Inventor
Songtao Shi
Wataru Sonoyama
Takayoshi Yamaza
Songlin Wang
Original Assignee
Univ Southern California
Songtao Shi
Wataru Sonoyama
Takayoshi Yamaza
Songlin Wang
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Southern California, Songtao Shi, Wataru Sonoyama, Takayoshi Yamaza, Songlin Wang filed Critical Univ Southern California
Priority to US12/514,051 priority Critical patent/US10232080B2/en
Publication of WO2008067488A2 publication Critical patent/WO2008067488A2/fr
Publication of WO2008067488A9 publication Critical patent/WO2008067488A9/fr
Publication of WO2008067488A3 publication Critical patent/WO2008067488A3/fr
Priority to US16/266,867 priority patent/US20190167846A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3804—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3839—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells characterised by the site of application in the body
    • A61L27/3843—Connective tissue
    • A61L27/3865—Dental/periodontal tissues
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • A61L27/3886—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells comprising two or more cell types
    • A61L27/3891—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells comprising two or more cell types as distinct cell layers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0003—Not used, see subgroups
    • A61C8/0004—Consolidating natural teeth
    • A61C8/0006—Periodontal tissue or bone regeneration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0018—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the shape
    • A61C8/0037—Details of the shape
    • A61C8/0043—Details of the shape having more than one root

Definitions

  • the present invention in general, relates to tissue re-generation.
  • the present invention relates to a new population of mesenchymal stem cells isolated from the root apical papilla of human teeth and methods for utilizing the stem cells in the regeneration of tooth,
  • the most important part of the tooth is the root which is required to support a (natural or artificial) crown; the crown alone cannot fulfill normal tooth function without a viable root.
  • the spatially and temporally organized microenvironment of the tooth bud and its surrounding tissues permits growth and development of the crown and roots, resulting in formation and eruption of the tooth (10).
  • Root development involves dentin formation, cementum generation, instruction of epithelium, and tooth eruption.
  • the re-generation of a whole tooth is highly complicated and technically challenging.
  • the lesser challenging goal of replacing a damaged crown with a synthetic crown has been widely applied in dental clinics with excellent therapeutic outcomes (11).
  • stem cell-mediated root regeneration offers opportunities to regenerate a bio-root and its associated periodontal tissues, which are necessary for maintaining the physiological function of teeth.
  • the inventors of the present invention have unexpectedly discovered and successfully isolated a novel population of mesenchymal stem cells from apical papilla (SCAP) that is capable of differentiating into odontoblastic/osteoblastic cells. Based on this discovery the inventors have developed tooth repair methods of the present invention.
  • SCAP apical papilla
  • the present invention provides a novel population of mesenchymal stem cells isolated from human root apical papilla tissue, wherein the stem cells are capable of differentiating into odontoblastic/osteoblastic cells.
  • the present invention provides a method for reconstructing a functional tooth in a subject, in which a bio-root periodontal complex is built up by postnatal stem cells including SCAP and periodontal ligament stem cells (PDLSCs), to which an artificial porcelain crown can then be affixed.
  • a bio-root periodontal complex is built up by postnatal stem cells including SCAP and periodontal ligament stem cells (PDLSCs), to which an artificial porcelain crown can then be affixed.
  • PDLSCs periodontal ligament stem cells
  • the hybrid strategy of this aspect of the present invention has at least the following advantages.
  • the present invention side-steps the challenging task of re-generating a whole tooth structure, and effectively enables recovery of tooth strength, function, and appearance in subjects who lack adequate bone structures.
  • Autologous dental stem cell engineering may also be applied to tooth regeneration in species having closely related dental tissues such as human, murine, swine, and simian.
  • Figure 1 shows the isolation of Stem Cells from Root Apical Papilla.
  • Human apical papilla tissue was positive for STRO-I, an early mesenchymal progenitor marker, staining by immunofluorescence (arrows).
  • B Single colonies were formed after human SCAP were plated at a low density (5 x 10 3 /T25 flask) and cultured for 10 days.
  • C When human SCAP were cultured in odontogenic/osteogenic inductive conditions containing L-ascorbate-2-phosphate, dexamethasone, and inorganic phosphate for 4 weeks, mineralized nodules were found by Alizarin red S staining.
  • E Eight weeks after transplantation in immunocompromised mice, human SCAP differentiated into odontoblasts (arrows) that formed dentin (D) on the surfaces of a hydroxyapatite tricalcium (HA) carrier.
  • FIG. 1 shows the characterization of human SCAP in comparison with DPSCs.
  • Figure 3 shows data that characterize the surface molecules of human SCAP
  • FIG 4 illustrates the combined human SCAP/PDLSC-mediated tissue regeneration.
  • A On the outside of the HA/TCP carrier (HA), PDLSCs can form structures resembling Sharpey's fibers (arrows) connecting with newly formed cementum (C) on the surface of HA/TCP particles (HA).
  • B Immunohistochemical staining showed that SCAP/PDLSC-generated tissues were positive for human specific mitochondria antibody staining (arrows).
  • Figure 5 shows swine SCAP/PDLSC-mediated root/periodontal structure as an artificial crown support for the restoration of tooth function in swine.
  • A Extracted minipig lower incisor and root-shaped HA/TCP carrier loaded with SCAP.
  • B Gelfoam containing 10 x 106 PDLSCs (open arrow) was used to cover the HA/SCAP (black arrow) and implanted into the lower incisor socket (open triangle).
  • C HA/SCAP- Gelfoam/PDLSCs were implanted into a newly extracted incisor socket. A post channel was pre-created inside the root shape HA carrier (arrow).
  • the present invention is based on the unexpected discovery of a novel population of mesenchymal stem cell isolated from the root apical papilla of human teeth.
  • the inventors of the present invention have successfully isolated and cultured this novel mesenchymal stem cell and developed methods for repairing damaged tooth by utilizing the mesenchymal stem cells of the present invention.
  • methods of the present invention utilizes the unique properties of mesenchymal stem cells in such a way that a bio-root may be grown into the subject's oral skeletal-muscular structure, which will then provide an anchoring point to affix conventional crowns.
  • the present invention provides a method for repairing a damaged tooth in a subject, having the general steps of: (1) providing a root-shaped biocompatible carrier formed in a shape resembling a root of the damaged tooth, loaded with SCAP, and coated with PDLSC, and wherein the carrier has an inner post channel space; (2) extracting the damaged tooth from the subject's oral cavity, wherein upon extraction of the damaged tooth, an extraction socket is formed in its place; (3) cleaning the extraction socket and implanting the root-shaped biocompatible carrier into the socket; (4) allowing sufficient time for the SCAP and PDLSC to form a bio-root incorporating the carrier; and (5) surgically exposing the biocompatible carrier and affixing a pre-fabricated crown resembling the damaged tooth onto the bio-root.
  • suitable biocompatible carrier may be made of any biocompatible material having physical properties such as strength, hardness, etc. that are suitable for use as a dental root.
  • exemplary biocompatible materials may include hydroxyapatite, tricalcium phosphate, or any other suitable biocompatible material commonly known in the art.
  • bio-root Once the bio-root is formed and become strong, it may be treated as a natural root. Conventional dental treatments such as crowning may then be used. Suitable crowns may be porcelain crowns, metal crowns, or any other types of crowns commonly known in the art. [0025] Having generally described the present invention, reference is now made to the following specific examples along with the accompanying figures to facilitate a full understanding of the present invention.
  • Root apical papilla was gently separated from the surface of the root, minced and digested in a solution of 3 mg/ml collagenase type I (Worthington Biochemicals Corp., Freehold, NJ) and 4 mg/ml dispase (Roche Diagnostic/Boehringer Mannheim Corp., Indianapolis, IN) for 30 minutes at 37 0 C.
  • Single cell suspensions of SCAP were obtained by passing through a 70 ⁇ m strainer (Falcon, BD Labware, Franklin Lakes, NJ) 3 seeded at 1 x 10 4 into 10 cm culture dishes (Costar, Cambridge, MA), and cultured with alpha-Modification of Eagle's Medium (GIBCO/Invitrogen, Carlsbad, CA) supplemented with 15% FBS (Equitech-Bio Inc., Kerrville, TX), 100 ⁇ M L-ascorbic acid 2-phosphate (WAKO, Tokyo, Japan), 2 mM L-glutamine (Biosource/Invitrogen), 100 U/ml penicillin and 100 ⁇ g/ml streptomycin at 37 0 C in 5% CO 2 .
  • Rabbit antibodies included anti-HSP90 (Santa Cruz Biotechnology, Inc., Santa
  • R-PE conjugated monoclonal anti-human antibodies include: CD 14, CDl 8, CD24, CD29, CD34, CD35, CD73, CD90, CD105, CD106, CD146, CD150, CD166 were purchased from Pharmingen/BD Bioscience (San Jose, CA) and monoclonal anti- human ALP was from Hybridoma Bank (Iowa University, Iowa).
  • telomerase activity in SCAP, DPSCs and BMSSCs was detected by using a quantitative telomerase detection kit (Allied Biotech, Inc., Ijamsville, MD) according to the manufacture's protocol for real time PCR. Briefly, the telomerase in the cell extract from 1 x 10 5 cells of SCAP, DPSCs, or BMSSCs added telomeric repeats (TTAGGG) onto the 3' end of the substrate oligonucleotide and iQ SYBR Green Supermix (BioRad Laboratories, Hercules, CA), and amplified with an iCycler iQ real-time PCR machine (BioRad Laboratories).
  • TTAGGG telomeric repeats
  • the generated PCR products are directly detected by measuring the increase in fluorescence caused by binding of SYBR Green to double-strand DNA and calculated by using an iCycler iQ software (BioRad Laboratories). Some cell extract was heated at 85 0 C for 10 minutes and used for negative control.
  • the real-time PCR condition was as follows; telomerase reaction for 20 minutes at 25 C, PCR initial activation step for 3 minutes at 95°C, 3-step cycling; denaturation for 10 seconds at 95 0 C, annealing for 30 seconds at 6O 0 C, extension for 3 minutes at 72°C, and cycle number 40 cycles.
  • SCAP and DPSCs were cultured at low density to form single cell-derived colonies and then were trypsinized and seeded at a density of 0.5 x 10 4 cells in 100-mm culture dishes at the first passage. Upon reaching confluency, the cells were trypsinized and seeded at the same cell density. The population doubling was calculated at every passage according to the equation: Iog2 (the number of harvested cells / the number of seeded cells). The finite population doublings were determined by cumulative addition of total numbers generated from each passage until the cells ceased dividing (20). The criteria for cell senescence are that cells do not divide for a month in culture and that over 60% of the cells are stained positive for beta-galactosidase (18).
  • STRO-I and ALP staining some of the cells were incubated with 100 ⁇ l of STRO-I supernatant (mouse IgM anti-human STRO-I) (16) or mouse IgGl anti-human bone/liver/kidney ALP (Hybridoma Bank) for 45 minutes on ice. After washing with 5% heat-inactivated FBS in HBSS at 4 ° C, they were reacted with R-PE conjugated goat F(ab')2 anti-mouse IgM ( ⁇ chain specific) (Biosource/Invitrogen) or anti-mouse IgG (H+L) (Southern Biotechnology Associates, Inc., Birmingham, AL) for 30 minutes on ice.
  • STRO-I supernatant mouse IgM anti-human STRO-I
  • mouse IgGl anti-human bone/liver/kidney ALP Hybridoma Bank
  • the cells were treated with 1 ⁇ g of R-PE conjugated mouse IgGl antimouse CD24 (BD Bioscience) for 45 minutes on ice. As negative controls, some of the cells were incubated with 1 ⁇ g of non-immune mouse IgM (Southern Biotechnology Associates, Inc.) or IgGl (BD Bioscience). After washing, all of the cells were then sorted on a FACSCalibur flow cytometer (BD Bioscience) by collecting 10,000 events, and analyzed by means of a Cell Quest software (BD Bioscience).
  • BD Bioscience FACSCalibur flow cytometer
  • Minipigs Six inbred male minipigs (4-8 month-old, weighing 20-40 kg) were obtained from the Institute of Animal Science of the Chinese Agriculture University. At this age, minipig incisors are still developing. Minipigs were kept under conventional conditions with free access to water and regularly supply of soft food. This study was reviewed and approved by the Animal Care and Use Committees of Capital University of Medical Sciences and the Institute of Dental and Craniofacial Research. Minipigs were anaesthetized with a combination of ketamine chloride (6 mg/kg) and xylazine (0.6 mg/kg) before the surgery. Minipig SCAP and PDLSCs were isolated and cultured the same as human SCAP and PDLSCs as mentioned above.
  • stem cell progenitors may contribute to root formation
  • human root apical papilla tissue on the exterior of the root foramen area demonstrated positive staining for mesenchymal stem cell surface molecule STRO-I ( Figure IA).
  • the root apical papilla might contain a population of stem/progenitor cells.
  • single-cell suspensions were generated from human root apical papillae collected from extracted third molars of 18- 20 years old adult volunteers ; following collagenase/dispase digestion.
  • SCAP lost the expression of CD24 with an up-regulated expression of alkaline phosphatase (ALP) ( Figure 3B).
  • ALP alkaline phosphatase
  • SCAP showed a significantly higher rate of bromodeoxyuridine (BrdU) uptake (Figure 2C), and increased number of population doublings (Figure 2D).
  • the SCAP population also demonstrated an elevated tissue regeneration capacity (Figure 2E), higher telomerase activity than that of DPSCs from the same tooth (Figure 2F), and an improved migration capacity in a scratch assay (Figure 2G), when compared to DPSCs from the same tooth.
  • Example 2 Surface molecule characterization of SCAP To characterize SCAP by surface molecules, flow cytometric analysis was used to demonstrate that SCAP at passage 1 expressed many surface markers including STRO- 1, ALP, CD24, CD29, CD73, CD90, CD105, CD106, CD146, CD166 and ALP but were negative for CD34, CD45, CD18 and CD150 (Figure 3A).
  • STRO-I and CD146 have been identified as early mesenchymal stem cell markers present on both BMMSCs and DPSCs (8, 16). It was found that CD24 appears to be a specific marker for SCAP, not detectable in other mesenchymal stem cells including DPSCs and BMMSCs (data not shown). In response to osteogenic induction conditions in culture, SCAP begin to down regulate their expression of CD24 while gaining expression of ALP ( Figure 3B).
  • SCAP derived from a developing tissue may represent a population of early progenitors that have advantages for use in tissue regeneration.
  • CT examination revealed a HA/SCAP-Gelfoam/PDLSC structure growing inside the socket with mineralized rootlike tissue formation and periodontal ligament space.
  • the surface of the implanted HA/SCAP-Gelfoam/PDLSC structure was surgically re-opened at three months post-implantation ; and a pre-fabricated porcelain crown resembling a minipig incisor was inserted and cemented into the pre-formed post channel inside the HA/TCP block (Figure 5F-H). After suture of the surgical opening, the porcelain crown was retained in situ and subjected to the process of tooth function for four weeks (Figure 51, J). CT and histologic analysis confirmed that the root/periodontal structure had regenerated (Figure 5K-M).
  • SCAP represent a novel population of multipotent stem cells as demonstrated by their capacity to develop into odontoblast-like cells and adipocytes in vitro. This cell population was found to express high levels of survivin and telomerase, which are both important molecules in mediating cell proliferation.
  • CD24 marker for undifferentiated SCAP is found to be downregulated following odontogenic differentiation.
  • the inventors also contemplate using allogeneic cells as another resource of stem cells for treating those aged individuals who have already had their wisdom teeth extracted, however the immunogenicity of these cells requires further study.
  • bio-roots show a lower compressive strength than that of natural swine root dentin, they seemed capable of supporting porcelain crown and resulted in normal functions. It may be possible to improve the compressive strength and hardness of the bio-roots by selecting optimal bioengineered materials and by optimizing the implanted stem cell numbers and quality.
  • Stem cell-mediated root regeneration hybridized with clinical crown technology offers a novel approach for functional tooth restoration. It has the advantage of benefiting from the availability of high-quality dental stem cells for autologous transplantation as well as long-term experience with clinical dental implant procedures.
  • the orofacial region is an open system for directly delivering stem cells for tissue engineering.
  • the minipigs example of the present invention offer an excellent translational model as a research tool for the concept of functional tooth regeneration and the feasibility of using autologous stem cells for transplantation.
  • Root or crown a developmental choice orchestrated by the differential regulation of the epithelial stem cell niche in the tooth of two rodent species. Development 130:1049-1057.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Transplantation (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Public Health (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Botany (AREA)
  • Zoology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Inorganic Chemistry (AREA)
  • Vascular Medicine (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Materials For Medical Uses (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)

Abstract

L'invention concerne un procédé destiné à reconstruire une dent fonctionnelle en utilisant un vecteur chargé d'une pluralité de cellules souches mésenchymateuses comprenant au moins une cellule souche parmi les cellules souches dérivées d'Apical Papilla (SCAP), de cellules souches de ligament parodontal (PDLSC) et de cellules souches de pulpe dentaire (DPSC). Le vecteur chargé de cellules souches mésenchymateuses est implanté dans un site à l'intérieur de la cavité buccale d'un sujet afin de former une bio-racine sur laquelle une couronne peut être fixée. Les cellules souches mésenchymateuses vont développer de nouveaux tissus parodontaux afin de stabiliser la bio-racine. Les procédés selon la présente invention sont particulièrement bénéfiques pour des sujets ne présentant pas une structure osseuse suffisamment bonne pour un traitement par couronne traditionnel.
PCT/US2007/085971 2006-11-29 2007-11-29 Régénération d'une dent fonctionnelle médiée par des cellules souches mésenchymateuses WO2008067488A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US12/514,051 US10232080B2 (en) 2006-11-29 2007-11-29 Mesenchymal stem cell-mediated function tooth regeneration
US16/266,867 US20190167846A1 (en) 2006-11-29 2019-02-04 Mesenchymal stem cell-mediated functional tooth regeneration

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US86775106P 2006-11-29 2006-11-29
US60/867,751 2006-11-29

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2007/085971 Continuation WO2008067488A2 (fr) 2006-11-29 2007-11-29 Régénération d'une dent fonctionnelle médiée par des cellules souches mésenchymateuses
US12/514,051 Continuation US10232080B2 (en) 2006-11-29 2007-11-29 Mesenchymal stem cell-mediated function tooth regeneration

Related Child Applications (4)

Application Number Title Priority Date Filing Date
PCT/US2007/085971 Continuation WO2008067488A2 (fr) 2006-11-29 2007-11-29 Régénération d'une dent fonctionnelle médiée par des cellules souches mésenchymateuses
US12/514,051 Continuation US10232080B2 (en) 2006-11-29 2007-11-29 Mesenchymal stem cell-mediated function tooth regeneration
US12/514,051 A-371-Of-International US10232080B2 (en) 2006-11-29 2007-11-29 Mesenchymal stem cell-mediated function tooth regeneration
US16/266,867 Continuation US20190167846A1 (en) 2006-11-29 2019-02-04 Mesenchymal stem cell-mediated functional tooth regeneration

Publications (3)

Publication Number Publication Date
WO2008067488A2 WO2008067488A2 (fr) 2008-06-05
WO2008067488A9 true WO2008067488A9 (fr) 2008-08-21
WO2008067488A3 WO2008067488A3 (fr) 2009-01-08

Family

ID=39468728

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/085971 WO2008067488A2 (fr) 2006-11-29 2007-11-29 Régénération d'une dent fonctionnelle médiée par des cellules souches mésenchymateuses

Country Status (2)

Country Link
US (2) US10232080B2 (fr)
WO (1) WO2008067488A2 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101970022A (zh) * 2008-03-12 2011-02-09 财团法人日本健康科学振兴财团 根管填充材料以及牙组织再生方法
JP5660896B2 (ja) * 2008-09-05 2015-01-28 学校法人 日本歯科大学 歯根・歯周組織ユニット形成方法、及び再生歯
US8470308B2 (en) * 2009-01-03 2013-06-25 Ray C. Wasielewski Enhanced medical implant comprising disrupted tooth pulp and tooth particles
US10328103B2 (en) 2009-01-03 2019-06-25 Ray C. Wasielewski Medical treatment composition comprising mammalian dental pulp stem cells
CN102292435B (zh) * 2009-01-23 2013-08-07 塞尔珍尼克斯生物科学公司 牙齿相关干细胞的新用途
WO2011030552A1 (fr) 2009-09-11 2011-03-17 独立行政法人国立長寿医療研究センター Obturateur de canal radiculaire pour dent non extraite et procédé d'extraction destiné à la régénération du tissu dentaire
WO2013106463A2 (fr) * 2012-01-09 2013-07-18 Old Dominion University Research Foundation Procédé et dispositif pour implants dentaires à forme de racine naturelle
US20150104428A1 (en) 2012-03-30 2015-04-16 University Of Southern California Compositions and Treatment Methods for Mesenchymal Stem Cell-Induced Immunoregulation
US9730771B2 (en) 2014-01-13 2017-08-15 Brock B. WESTOVER Endosseous dental implant assembly
CN108753707A (zh) * 2018-06-11 2018-11-06 南京泰盛生物科技有限公司 一种通过细胞表面标记特异性富集的人牙根尖乳头干细胞亚群及其干性检测方法
US20220378848A1 (en) * 2019-07-29 2022-12-01 Jill Wade Compositions and methods of using multipotent stem cells to reduce disease and enhance wellness

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4671770A (en) * 1984-04-03 1987-06-09 Denpac Corp. High strength porcelain dental prosthetic device
FR2784284B1 (fr) * 1998-10-13 2000-12-15 Natural Implant Sa Procede de preparation d'un implant dentaire par immersion dans une culture de cellules mesenchymateuses, dispositif de culture de cellules pour la preparation dudit implant et implant obtenu
AU7707801A (en) * 2000-07-21 2002-02-05 Us Health Adult human dental pulp stem cells in vitro and in vivo
AU2001288018A1 (en) * 2000-09-05 2002-03-22 Technion Research And Development Foundation Ltd. Methods of repairing longitudinal bone defects
DE602005012081D1 (de) * 2005-07-29 2009-02-12 Univ Bonn Verfahren zur Isolierung von Stammzellen aus ein kissenformiges Gewebe der Zähne

Also Published As

Publication number Publication date
US20100196854A1 (en) 2010-08-05
WO2008067488A2 (fr) 2008-06-05
WO2008067488A3 (fr) 2009-01-08
US10232080B2 (en) 2019-03-19
US20190167846A1 (en) 2019-06-06

Similar Documents

Publication Publication Date Title
US20190167846A1 (en) Mesenchymal stem cell-mediated functional tooth regeneration
Sonoyama et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine
US9682107B2 (en) Postnatal stem cells and uses thereof
Honda et al. Dental follicle stem cells and tissue engineering
JP5069572B2 (ja) 間葉系細胞の製造方法、歯の製造方法及び歯形成用間葉系細胞
ES2423898T3 (es) Citoblastos de pulpa dental de seres humanos adultos in vitro e in vivo
Huang et al. The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering
Guo et al. Dental follicle cells and treated dentin matrix scaffold for tissue engineering the tooth root
Honda et al. Stem cells isolated from human dental follicles have osteogenic potential
US20090035376A1 (en) Stem cells obtained from pulp of deciduous or permanent teeth and of dental germ, able to produce human bone tissue
Lacerda-Pinheiro et al. Concomitant multipotent and unipotent dental pulp progenitors and their respective contribution to mineralised tissue formation
AU2001277078A1 (en) Adult human dental pulp stem cells in vitro and in vivo
JP2012179123A (ja) 間葉系幹細胞を含んでなる根管充填材、及びこれを用いた歯組織再生方法
EP1934332B1 (fr) Procede de differentiation des cellules souches et son utilisation pour le traitement d'etats dentaires
US20130029292A1 (en) Method of implanting mesenchymal stem cells for natural tooth regeneration in surgically prepared extraction socket and compositions thereof
Komaki Pericytes in the periodontal ligament
Iwata et al. In vitro proliferation of periodontal ligament-like tissue on extracted teeth
US9168139B2 (en) Vertical bone augmentation using endothelial progenitor cells
WO2010021162A1 (fr) Préparation de cellules pour régénération de tissu osseux
RU2265445C1 (ru) Биотрансплантат, способ его получения (варианты) и способ лечения заболеваний пародонта
CA2809164C (fr) Cellules souches postnatales et utilisations
Wang et al. Bioengineering of Roots and Periodontal Tissues
Stella et al. Stem cells in the future of dental care
JP2020036550A (ja) 歯根膜又は靭帯細胞の作製方法
Gay Isolation And Characterization Of Human Periodontal Ligament Stem Cells

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07864923

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07864923

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 12514051

Country of ref document: US